Cell and Organ Transplantology. 2023; 11(2):114-121.
DOI: 10.22494/cot.v11i2.157
Mesenchymal stem cell therapy modulates macrophage dynamics in ARDS-associated liver injury in rats
Redko O.
, Dovgalyuk A., Kramar S., Ohinska N., Nebesna Z., Korda M.
- I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
Abstract
Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary condition characterized by severe hypoxemia and respiratory failure. Beyond its devastating impact on the lungs, ARDS often triggers systemic responses affecting vital organs throughout the body. One such organ commonly affected is the liver, which experiences various degrees of injury during the course of ARDS. Pathophysiological changes in liver during ARDS, particularly polarization of Kupffer cells during the disease and its treatment, have drawn increasing attention.
Purpose. To explore the macrophage transformation in liver injury associated with ARDS and investigate the potential of multipotent mesenchymal stromal/stem cell (MMSCs) therapy as a means to modulate macrophage responses and mitigate liver injury.
Methods. 72 mature male Wistar rats were randomly allocated to nine experimental groups as follows: the control group, groups assessed at 3 days, 7 days, and 28 days following intranasal lipopolysaccharide (LPS) administration, groups that received 24 hours of LPS followed by 2 days of human umbilical cord-derived multipotent mesenchymal stromal cells (hUC-MMSCs), groups exposed to 4 days of LPS and 3 days of hUC-MMSCs, groups subjected to 14 days of LPS and 14 days of hUC-MMSCs, groups treated with LPS 21 days and 7 days with hUC-MMSCs injection, and a control group assessed 3 days after hUC-MMSCs injection. For the administration of hUC-MMSCs, intraperitoneal injections were performed at a dose of 1×106 cells/kg body weight. Immunohistochemistry was used to analyze macrophage subpopulations in liver tissue for CD68 as a pan-macrophage marker, CD86 for the identification of M1 macrophages, CD163 – for the identification of M2 macrophages.
Results. Early ARDS stages showed increased M1 macrophages, indicating pro-inflammatory responses, while later stages showed M2 macrophage activation, suggestive of anti-inflammatory properties and tissue repair roles. hUC-MMSCs administration facilitated the transition from M1 to M2 macrophages, promoting an anti-inflammatory milieu.
Conclusion. hUC-MMSCs demonstrate the potential to modulate macrophage polarization into M2 anti-inflammatory phenotype. Such findings reflect one of the mechanisms of MMSCs action which holds practical significance for future ARDS therapies, aiming to mitigate excessive inflammation and enhance tissue repair.
Key words: aacute respiratory distress syndrome; liver injury; multipotent mesenchymal stromal cells; macrophage polarization; inflammation, immunomodulation
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Redko O, Dovgalyuk A, Kramar S, Ohinska N, Nebesna Z, Korda M. Mesenchymal stem cell therapy modulates macrophage dynamics in ARDS-associated liver injury in rats. Cell Organ Transpl. 2023; 11(2):114-121. Available from: https://doi.org/10.22494/cot.v11i2.157
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